Reversible sulfonation

In contrast to aromatic nitration and other electrophilic aromatic substitutions aromatic sulfonation is reversible. Sulfonation takes place in strong acidic conditions and desulfonation is the mode of action in a hot aqueous acid. 

Scheme 8.39. A representation of the reversible sulfonation of phenol to provide both ortho-and para-hydroxybenzenesulfonic acids. At 20°C with 98% sulfuric acid (H2SO4), the ratio of para- to cjrfAo-substitution is about 1 1. At 100°C, the ratio of para to ortho is about 9 1.

Aromatic sulfonation is readily reversible. The reaction of sulfur trioxide with water to give sulfuric acid is so exothermic that heating benzenesulfonic acid in dilute aqueous acid completely reverses sulfonation. 

The reversibility of sulfonation may be used to control further aromatic substitution processes. The ring carbon containing the substituent is blocked from attack, and electrophiles are directed to other positions. Thus, the sulfonic acid group can be introduced to serve as a directing blocking group and then removed by reverse sulfonation. Synthetic applications of this strategy will be discussed in Section 16-5. 

Reversible sulfonation allows the efficient synthesis of ortho-disubstituted benzenes... 

A clever solution makes use of reversible sulfonation (Section 15-10) as a blocking procedure. Both the substituent and the electrophile are sterically bulky hence, (1,1-dimethylethyl)benzene is sulfonated almost entirely para, blocking this carbon from further electrophilic attack. Nitration now can occur only ortho to the alkyl group. Heating in aqueous acid removes the blocking group and completes the synthesis. 

This is an exothermic, reversible, homogeneous reaction taking place in a single liquid phase. The liquid butadiene feed contains 0.5 percent normal butane as an impurity. The sulfur dioxide is essentially pure. The mole ratio of sulfur dioxide to butadiene must be kept above 1 to prevent unwanted polymerization reactions. A value of 1.2 is assumed. The temperature in the process must be kept above 65°C to prevent crystallization of the butadiene sulfone but below lOO C to prevent its decomposition. The product must contain less than 0.5 wt% butadiene and less thM 0.3 wt% sulfur dioxide. 

The higjily water-soluble dienophiles 2.4f and2.4g have been synthesised as outlined in Scheme 2.5. Both compounds were prepared from p-(bromomethyl)benzaldehyde (2.8) which was synthesised by reducing p-(bromomethyl)benzonitrile (2.7) with diisobutyl aluminium hydride following a literature procedure2.4f was obtained in two steps by conversion of 2.8 to the corresponding sodium sulfonate (2.9), followed by an aldol reaction with 2-acetylpyridine. In the preparation of 2.4g the sequence of steps had to be reversed Here, the aldol condensation of 2.8 with 2-acetylpyridine was followed by nucleophilic substitution of the bromide of 2.10 by trimethylamine. Attempts to prepare 2.4f from 2.10 by treatment with sodium sulfite failed, due to decomposition of 2.10 under the conditions required for the substitution by sulfite anion. 

IS reversible but can be driven to completion by several techniques Removing the water formed m the reaction for example allows benzene sulfonic acid to be obtained m vir tually quantitative yield When a solution of sulfur trioxide m sulfuric acid is used as the sulfonatmg agent the rate of sulfonation is much faster and the equilibrium is dis placed entirely to the side of products according to the equation... 

As in most electrophilic reactions, the abiUty to stabilize the positive charge generated by the initial addition strongly affects the relative rates. MX reacts faster than OX and PX because both methyl groups work in conjunction to stabilize the charge on the next-but-one carbon. Sulfonation was, at one time, used to separate MX from the other Cg aromatic isomers. MX reacts most rapidly to form the sulfonic acid which remains in the aqueous phase. The sulfonation reaction is reversible, and MX can be regenerated. 

Substitution Reactions on Side Chains. Because the benzyl carbon is the most reactive site on the propanoid side chain, many substitution reactions occur at this position. Typically, substitution reactions occur by attack of a nucleophilic reagent on a benzyl carbon present in the form of a carbonium ion or a methine group in a quinonemethide stmeture. In a reversal of the ether cleavage reactions described, benzyl alcohols and ethers may be transformed to alkyl or aryl ethers by acid-catalyzed etherifications or transetherifications with alcohol or phenol. The conversion of a benzyl alcohol or ether to a sulfonic acid group is among the most important side chain modification reactions because it is essential to the solubilization of lignin in the sulfite pulping process (17). 

Subtractive dye precursors (couplers) that could be immobilized in each of the silver containing layers were sought, so that dye formation in all layers could proceed simultaneously rather than successively. The first of these to be commercialized were in Agfacolor Neue and Ansco Color films, introduced soon after Kodachrome film. These reversal working films contained colorless couplers that were immobilized (ballasted) by the attachment of long paraffinic chains. The addition of sulfonic or carboxyUc acid groups provided the necessary hydrophilicity to make them dispersible as micelles in aqueous gelatin. 

As in the nitration of naphthalene, sulfonation gives the 1-substituted naphthalene. However, because the reverse reaction (desulfonation) is appreciably fast at higher temperatures, the thermodynamically controlled product, naphthalene-2-sulfonic acid, can also be obtained. Thus it is possible to obtain either of the two possible isomers of naphthalene sulfonic acid. Under kineticaHy controlled conditions naphthalene-l-sulfonic acid [85-47-2] (82) is obtained thermodynamic control gives naphthalene-2-sulfonic acid [120-18-3] (83). 

Commercially, sulfonic acid ion-exchange resins are used in fixed-bed reactors to make these tertiary alkyl ethers (14). Since the reaction is very selective to tertiary olefins and also reversible, a two-step procedure is also used to recover commercially pure tertiary olefins from mixed olefin process streams. The corresponding tertiary alkyl ether is produced in the olefin mixture and then easily separated from the unreacted olefins by simple fractionation. The reaction is then reversed in a second step to make a commercially pure tertiary olefin, usually isobutylene or isoamylene. 

The relative stability of the intermediates determines the position of substitution under kinetically controlled conditions. For naphthalene, the preferred site for electrophilic attack is the 1-position. Two factors can result in substitution at the 2-position. If the electrophile is very bulky, the hydrogen on the adjacent ring may cause a steric preference for attack at C-2. Under conditions of reversible substitution, where relative thermodynamic stability is the controlling factor, 2-substitution is frequently preferred. An example of this behavior is in sulfonation, where low-temperature reaction gives the 1-isomer but at elevated temperatures the 2-isomer is formed. ... 

The sulfonation of an aromatic ring with SO3 and H2S04 is reversible. That is, heating benzenesulfonic acid with H2SO4 yields benzene. Show the mechanism of the desulfonation read ion. What is the electrophile ... 

Benzothiepins 13 and their 2,3-dihydro precursors 12 can be oxidized by two equivalents of 3-chloroperoxybenzoic acid to afford the sulfones 15 and 14, respectively, in moderate to good yields.2,9 83 Sulfones 15 can be prepared using two routes, the reverse order (oxidation, followed by elimination) also being possible (see Section 2.1.2.1. for a description of the elimination reactions). The preferred route must be decided for individual cases. 

The overall mechanism of the substitution proper in azo coupling reactions can be summarized as shown in Scheme 12-83. This scheme is simplified, insofar as charges in the coupling component and additional charges (e.g., of sulfonate groups) in the diazo compound are neglected, and it does not include information on reversibility. 

In principle, sulfonyl compounds bearing highly-electron-accepting substituents are able to transfer the sulfonyl group as an electrophile. Thus, the exchange of aryl substituents in methyl aryl sulfones under catalysis of trifluoromethanesulfonic acid takes place258 (equation 46). This reaction represents a further example for the reversibility of Friedel-Crafts reactions. 

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